We propose to study the effects of dietary vitamin E and selenium levels on the development of oxygen-induced lung damage in the rodent utilizing several key interacting biochemical parameters. Specifically, we propose to determine the relative changes in the levels of lung glutathione peroxidase, catalase and superoxide dismutase as an index of formation of the various peroxidation products resulting from molecular interactions of oxygen at above-ambient tensions with lung tissue. The dose response pattern of the above-mentioned lung antioxidant protective enzyme systems to dietary vitamin E and selenium for both acute and chronic above-ambient inspired oxygen exposures will be determined. Also, the effects of above-ambient oxygen tensions on lung lysosomal enzyme release and lung prostaglandin metabolism will be evaluated. The following additional lung biochemical parameters will be monitored: (1) lipid peroxidation from malonaldehyde formation, (2) lysosomal labilization from release of cathepsin C and phospholipase A and (3) prostaglandin metabolism from changes in the levels of lung prostaglandin synthetase, prostaglandin dehydrogenase and tissue prostanglandin levels. The ability of non-steroidal anti-inflammatory agents to modify oxygen-induced lung damage will be quantitatively determined by measuring the effects of these agents on the aforementioned biochemical pathways. Finally, we plan to develop clinical methods for the determination of oxygen-induced lung damage by measurements of products of lung lipid peroxidation in expired air and/or blood in patients receiving high inspired oxygen concentrations (in order to maintain blood oxygenation). Based on the earlier experimental results, we then plan to design clinical trials of antioxidant compounds including non-steroidal anti- inflammatory agents.